Ester-linked surface modifying macromolecules

ABSTRACT

The invention relates to ester-linked surface-modifying macromolecules and admixtures thereof as shown below by the representative compounds. The admixtures can be used in industrial and medical applications where enhanced surface properties are desirable (e.g., surface properties reducing or preventing biofouling, immobilization of biomolecules, or denaturation of certain biomolecules).

FIELD OF THE INVENTION

The invention relates to surface-modifying macromolecules and admixturesthereof with base polymers. The admixtures can be used in applicationswhere enhanced surface properties (e.g., surface properties reducing orpreventing biofouling, immobilization of biomolecules, or denaturationof certain biomolecules) are desired, e.g., in industrial and medicalapplications.

BACKGROUND OF THE INVENTION

Wetted surfaces can be susceptible to interaction with biologicalagents, such as proteins, nucleic acids, and living organisms. Theseinteractions can lead to degradation of adsorption of the biologicalagent (e.g., a protein or a nucleic acid). These interactions can alsolead to surface fouling by water constituents such as biomolecules,living organisms (e.g., bacteria), dissolved inorganic or organiccompounds, colloids, and suspended solids. Biofouling can beattributable to accumulated extracellular materials such as solublemicrobial products and extracellular polymeric substances such aspolysaccharides and proteins (see, e.g., Asatekin et al., Journal ofMembrane Science, 285:81-89, 2006). For example, membranes that are usedfor industrial water filtration or in medical applications (e.g., indialysis) can suffer fouling due to e.g., adsorption of proteins,attachment of suspended particles, or precipitated salts to themembrane. Still other examples of fouling in biomedical applications cangenerally result from the adherence of, e.g., cells and pathogens to thesurface of a medical device (e.g., a catheter or other implantablemedical device), and such fouling can have potentially adverse outcomes.Fouling can also be evident on the hulls of marine vessels, which canbecome coated with marine organisms or their secretions.

Accordingly, compositions and admixtures that have surface propertiesreducing or preventing biofouling, immobilization of biomolecules, ordenaturation of certain biomolecules can be useful in diverseapplications in industry and medicine.

SUMMARY OF THE INVENTION

In general, the present invention provides ester-linkedsurface-modifying macromolecules.

In a first aspect, the invention provides a compound of formula (I):

where

each F_(T) is independently a surface active group selected from thegroup consisting of polydimethylsiloxanes, hydrocarbons,polyfluoroorgano, and combinations thereof;

X₁ is H, CH₃, or CH₂CH₃;

each of X₂ and X₃ is independently H, CH₃, CH₂CH₃, or F_(T);

each of L₁ and L₂ is independently a bond, an oligomeric linker, or alinker with two terminal carbonyls; and

n is an integer from 5 to 50.

In formula (I), each of L₁ and L₂ can be a bond. Each of L₁ and L₂ canbe a linker with two terminal carbonyls. Each of L₁ and L₂ can be anoligomeric linker. The oligomeric linker can include (alkylene oxide),(e.g., (ethylene oxide)_(z)), in which z is an integer from 2 to 20(e.g., from 2 to 18, from 2 to 16, from 2 to 14, or from 2 to 12).

In formula (I), the compound can have a structure of formula (I-A):

in which each of m1 and m2 is independently an integer from 0 to 50.

In formula (I-A), m1 can be 5, 6, 7, 8, 9, or 10. In formula (I-A), m2can be 5, 6, 7, 8, 9, or 10. In formula (I-A), m1 can be equal to m2(e.g., each of m1 and m2 can be 6, or each of m1 and m2 can be 0).

In formula (I) or (I-A), n is 5, 6, 7, 8, 9, or 10 (e.g., n can be 8).

In formula (I) or (I-A), X₂ can be H, CH₃, or CH₂CH₃. In formula (I) or(I-A), X₂ can be F_(T). In formula (I) or (I-A), X₃ can be F_(T). EachF_(T), when present, can be independently a polyfluoroorgano group. Forexample, each F_(T), when present, can be independently—(O)_(q)—[C(═O)]_(r)—(CH₂)_(o)(CF₂)_(p)CF₃,

in which

q is 0, and r is 1, or q is 1, and r is 0;

o is from 0 to 2; and

p is from 0 to 10;

provided that the compound does not contain —O—O—.

In formula (I) or (I-A), each F_(T) can contain (CF₂)₅CF₃. In formula(I) or (I-A), X₁ can be CH₂CH₃.

In a second aspect, the invention provides a compound of formula (II),

in which

each F_(T) is independently a surface active group selected from thegroup consisting of polydimethylsiloxanes, hydrocarbons,polyfluoroorgano, and combinations thereof;

each of X₁, X₂, and X₃ is independently H, CH₃, CH₂CH₃, or F_(T);

each of L₁ and L₂ is independently a bond, an oligomeric linker, or alinker with two terminal carbonyls; and

each of n1 and n2 is independently an integer from 3 to 50.

In formula (II), each of L₁ and L₂ can be a bond. In formula (II), eachof L₁ and L₂ can be a linker with two terminal carbonyls. In formula(II), each of L₁ and L₂ can be norbornene-dicarbonyl or terephthaloyl.In formula (II), each of L₁ and L₂ can be an oligomeric linker. Informula (II), the oligomeric linker can contain (alkylene oxide), (e.g.,(ethylene oxide)_(z)), in which z can be an integer from 2 to 20 (e.g.,from 2 to 18, from 2 to 16, from 2 to 14, or from 2 to 12).

In formula (II), the compound can have a structure of formula (II-A),

in which each of m1 and m2 is independently an integer from 0 to 50.

In formula (II-A), m1 can be 5, 6, 7, 8, 9, or 10. In formula (II-A), m2can be 5, 6, 7, 8, 9, or 10. In formula (II), m1 can be equal to m2(e.g., each of m1 and m2 can be 3). In formula (II-A), the sum of n1,n2, m1, and m2 can be an integer from 5 to 15.

In formula (II) or (II-A), n1 can be 4. In formula (II) or (II-A), n2can be 5.

In formula (II) or (II-A), X₂ can be H, CH₃, or CH₂CH₃. In formula (II)or (II-A), X₂ can be F_(T). In formula (II) or (II-A), X₁ can be F_(T).In formula (II) or (II-A), X₃ can be F_(T). In formula (II) or (II-A),each F_(T), when present, can be independently a polyfluoroorgano group.For example, each F_(T), when present, can be independently—(O)_(q)—[C(═O)]_(r)—(CH₂)_(o)(CF₂)_(p)CF₃,

in which

q is 0, and r is 1, or q is 1, and r is 0;

o is from 0 to 2; and

p is from 0 to 10;

provided that the compound does not contain —O—O—.

In formula (II) or (II-A), each F_(T) can include —(CF₂)₅CF₃.

In a third aspect, the invention provides a compound of formula (III):G-(A)_(m)-[B-A]_(n)-B-G  (III)

in which

-   -   (i) A comprises polyurethane, polyurea, polyamide, polyalkylene        oxide, polycarbonate, polyester, polylactone, polysilicone,        polyethersulfone, polyalkylene, polyvinyl, polypeptide        polysaccharide, or an ether-linked or amine-linked segments        thereof (e.g., the segment in this case can refer to a repeating        unit in the listed oligomer);    -   (ii) B is a bond, an oligomeric linker, or a linker with two        terminal carbonyls; and    -   (iii) G is (a) a surface active group comprising a        polyfluoroorgano group or (b) H;    -   (iv) n is an integer from 1 to 10; and    -   (v) m is 0 or 1;    -   provided that at least one G is the surface active group        comprising a polyfluoroorgano group.

In some embodiments of formula (III), the compound has a structure offormula (IV):G-(A)_(m)-[B-A]_(n)-B-G  (IV)

in which

-   -   (i) A comprises a polysiloxane;    -   (ii) B comprises is a bond, an oligomeric linker, or a linker        with two terminal carbonyls; and    -   (iii) G is (a) a surface active group comprising a        polyfluoroorgano group or (b) H;    -   (iv) n is an integer from 1 to 10; and    -   (v) m is 0 or 1;    -   provided that at least one G is the surface active group        comprising a polyfluoroorgano group.

In formula (III) or (IV), m can be 0.

In formula (III) or (IV), m can be 1. The surface-modifyingmacromolecule of formula (III) can be a compound of formula (III-A):G-A-[B-A]_(n)-G  (III-A).

In formula (III) or (IV), m can be 0. The surface-modifyingmacromolecule of formula (III) can be a compound of formula (III-B):G-[B-A]_(n)-B-G  (III-B).

In formula (III), (IV), (III-A), or (III-B), each B can be a linker withtwo terminal carbonyls.

In formula (III), (IV), (III-A), or (III-B), each B can be a bond. Informula (III), (IV), (III-A), or (III-B), the bond connecting G and Bcan be an oxycarbonyl bond (e.g., an oxycarbonyl bond in an ester). Informula (III), (IV), (III-A), or (III-B), n can be 1 or 2.

The surface-modifying macromolecule of formula (III) can be a compoundof formula (III-C):G-A-G  (III-C).

In formula (III), (IV), (III-A), (III-B), or (III-C), A can be anoligomeric segment.

In formula (III), (III-A), (III-B), or (III-C), A can containhydrogenated polybutadiene, hydrogenated polyisoprene, poly((2,2-dimethyl)-1,3-propylene carbonate), polybutadiene, poly(diethylene glycol)adipate, poly (hexamethylene carbonate), poly(ethylene-co-butylene), (diethylene glycol-ortho phthalic anhydride)polyester, (1,6-hexanediol-ortho phthalic anhydride) polyester,(neopentyl glycol-ortho phthalic anhydride) polyester, a polysiloxane,bisphenol A ethoxylate, or poly(ethylene oxide)-b-poly(propyleneoxide)-b-poly(ethylene oxide) (e.g., Pluronic®).

In formula (III), (III-A), (III-B), or (III-C), A can containhydrogenated polybutadiene. In formula (III), (III-A), (III-B), or(III-C), A can contain hydrogenated polyisoprene.

In formula (III), (IV), (III-A), (III-B), or (III-C), A can contain apolysiloxane (e.g., A can contain a triblock copolymerPEG-b-(polysiloxane)-b-PEG).

In formula (III), (IV), (III-A), (III-B), or (III-C), each B can be abond. Each B can be a linker with two terminal carbonyls. Each B can benorbornene-dicarbonyl or terephthaloyl.

In formula (III), (IV), (III-A), (III-B), or (III-C), both G can be thesurface active group comprising a polyfluoroorgano group. Alternatively,in formula (III), (IV), (III-A), (III-B), or (III-C), one G can be thesurface active group comprising a polyfluoroorgano group, and the otherG can be H.

In formula (III), (IV), (III-A), (III-B), or (III-C), the surface activegroup can be a polyfluoroorgano (e.g., a polyfluoroalkyl). For example,the surface active group can be—(O)_(q)—[C(═O)]_(r)—(CH₂)_(o)(CF₂)_(p)CF₃,

in which

q is 0, and r is 1, or q is 1, and r is 0;

o is from 0 to 2; and

p is from 0 to 10;

provided that the compound does not contain —O—O—.

The compound of any aspect can have a theoretical molecular weight ofless than 10,000 Daltons. The compound of any aspect can have a thermaldegradation temperature of from 200° C. to 400° C.

In a related aspect, the invention provides a composition containing oneor more compounds of formula (III), (IV), (III-A), (III-B), or (III-C).

In a fourth aspect, the invention provides an admixture containing abase polymer and the compound of any one of the first aspect, secondaspect, or third aspect (e.g., from 0.005% to 15% (w/w) of the compoundof any one of the first aspect, second aspect, or third aspect).

The base polymer can be selected from the group consisting ofpolyurethanes, polysulfones, polycarbonates, polyesters, polyamides,polyimides, polyalkylenes (e.g., polyethylene, polypropylene,polystyrene, polybutadiene, polyisoprene,poly(acrylonitrile-butadienestyrene), polymethylmethacrylate,polyvinylacetate, polyacrylonitrile, or polyvinyl chloride),polysilicone, polysaccharides (e.g., cellulose, cellulose acetate,cellulose diacetate, or cellulose triacetate) and copolymers thereof(e.g., polyethylene terephtahate), and blends thereof.

The base polymer can be selected from the group consistin ofpolyethylene, polypropylene, polystyrene, polybutadiene, polyisoprene,poly(acrylonitrile-butadienestyrene), cellulose, cellulose acetates,cellulose diacetates, cellulose triacetates, polyethylene terephtahate.

The base polymer can be selected from the group consistin of polyamides,polyurethanes, polysilicones, polysulfones, polyalkylenes, polyesters,polypeptides, and polysaccharides.

The base polymer can be selected from the group consisting ofpolyurethanes, polysulfones, polycarbonates, polyesters, polyamides,polyethylene, polypropylene, polystyrene, polysilicone,poly(acrylonitrile-butadiene-styrene), polybutadiene, polyisoprene,polymethylmethacrylate, polyvinylacetate, polyacrylonitrile, polyvinylcloride, polyethylene terephtahate, cellulose, cellulose acetates, andcellulose di- and tri-acetates.

Definitions

The term “alkyl,” as used herein, refers to a branched or unbranchedsaturated hydrocarbon group, having from 1 to 10 carbon atoms (C₁₋₁₀).An alkyl may optionally include a monocyclic, bicyclic, or tricyclicring system, in which each ring desirably has three to six members. Thealkyl group may be unsubstituted or substituted with one, two, or threesubstituents independently selected from the group consisting of alkoxy,aryloxy, alkylthio, arylthio, halogen, disubstituted amino, and ester.

The term “alkylene,” as used herein, refers to divalent alkyl groups.

The term “alkenyl,” as used herein, refers to a branched or unbranchedhydrocarbon group containing one, two, or three double bonds, desirablyhaving from 2 to 10 carbon atoms (C₂₋₁₀). A C₂₋₁₀ alkenyl may optionallyinclude non-aromatic monocyclic, bicyclic, or tricyclic rings, in whicheach ring desirably has five or six members. The C₂₋₁₀ alkenyl group maybe unsubstituted or substituted with one, two, or three substituentsindependently selected from the group consisting of alkoxy, aryloxy,alkylthio, arylthio, halogen, disubstituted amino, and ester.

The term “alkynyl,” as used herein, refers to a branched or unbranchedhydrocarbon group containing one or more triple bonds, desirably havingfrom 2 to 10 carbon atoms (C₂₋₁₀). The C₂₋₁₀ alkynyl group may beunsubstituted or substituted with one, two, or three substituentsindependently selected from the group consisting of alkoxy, aryloxy,alkylthio, arylthio, halogen, disubstituted amino, and ester.

The term “aryl,” as used herein, represents a mono-, bicyclic, ormulticyclic carbocyclic or heterocyclic ring system having one or twoaromatic rings. Carbocyclic aryl groups may include from 6 to 10 carbonatoms. All atoms within an unsubstituted carbocyclic aryl group arecarbon atoms. Non-limiting examples of carbocyclic aryl groups includephenyl, naphthyl, 1,2-dihydronaphthyl, 1,2,3,4-tetrahydronaphthyl,fluorenyl, indanyl, indenyl, etc. Heterocyclic aryl groups (e.g.,heteroaryl groups) may include 1, 2, 3, or 4 heteroatoms selected fromthe group consisting of N, O, and S, provided that at least one aromaticring includes at least one heteroatom. Heteroaryl groups may includefrom 1 to 9 carbon atoms. Non-limiting examples of heterocyclic arylgroups include benzimidazolyl, benzofuryl, benzothiazolyl, benzothienyl,benzoxazolyl, furyl, imidazolyl, indolyl, isoindazolyl, isoquinolinyl,isothiazolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, purinyl,pyrrolyl, pyridinyl, pyrazinyl, pyrimidinyl, qunazolinyl, quinolinyl,thiadiazolyl (e.g., 1,3,4-thiadiazole), thiazolyl, thienyl, triazolyl,tetrazolyl, etc. The aryl group may be optionally substituted with one,two, three, four, or five substituents independently selected from thegroup consisting of: alkyl; alkenyl; alkynyl; alkoxy; alkylsulfonyl;aryloxy; halo; nitro; silyl; and cyano.

The term “base polymer,” as used herein, refers to a polymer having atheoretical molecular weight of greater than or equal to 20 kDa (e.g.,greater than or equal to 50 kDa, greater than or equal to 75 kDa,greater than or equal to 100 kDa, greater than or equal to 150 kDa, orgreater than 200 kDa). Non-limiting examples of base polymers includepolyurethanes, polysulfones, polycarbonates, polyesters, polyamides,polyimides, polyalkylenes (e.g., polyethylene, polypropylene,polystyrene, polybutadiene, polyisoprene,poly(acrylonitrile-butadienestyrene), polymethylmethacrylate,polyvinylacetate, polyacrylonitrile, polyvinyl chloride), polysilicone,polysaccharides (e.g., cellulose, cellulose acetate, cellulosediacetate, or cellulose triacetate) and copolymers thereof (e.g.,polyethylene terephtahate).

The term “heteroalkyl,” as used herein, refers to an alkyl, alkenyl, oralkynyl, which further includes 1, 2, 3, or 4 heteroatoms, eachheteroatom independently selected from the group consisting of nitrogen,oxygen, and sulfur. Accordingly, heteroalkyl can be a C₁₋₁₀ heteroalkyl.

The term “linker with two terminal carbonyls,” as used herein, refers toa divalent group having a molecular weight of between 56 Da and 1,000Da, in which the first valency belongs to a first carbonyl, and a secondvalency belongs to a second carbonyl. Within this linker, the firstcarbonyl is bonded to a first carbon atom, and the second carbonyl isbonded to a second carbon atom. The linker with two terminal carbonylscan be non-polymeric (e.g., cycloalkylene-dicarbonyl (e.g.,norbornene-dicarbonyl), benzene-dicarbonyl, biphenyl-dicarbonyl,alkylene-dicarbonyl (e.g., succinoyl, glutaryl, adipoyl, pimeloyl,suberoyl, etc.)).

The term “molecular weight,” as used herein, refers to a theoreticalweight of an Avogadro number of molecules of identical composition. Aspreparation of a surface-modifying macromolecule can involve generationof a distribution of compounds, the term “molecular weight” refers to anidealized structure determined by the stoichiometry of the reactiveingredients. Thus, the term “molecular weight,” as used herein, refersto a theoretical molecular weight.

The term “oligomeric linker,” as used herein, refers to a divalent groupcontaining from two to fifty bonded to each other identical chemicalmoieties. The chemical moiety can be an alkylene oxide (e.g., ethyleneoxide).

The term “oligomeric segment,” as used herein, refers to a length of arepeating unit or units that is less than about 200 monomeric units.Oligomeric segment can have a theoretical molecular weight of less thanor equal to 10,000 Daltons, but preferably <7,000 Daltons and in someexamples, <5,000 Daltons. The surface-modifying macromolecule of theinvention can be formed from an oligomeric segment diol, triol, ortetraol to give a compound of formula (I), (II), (III), or (IV).Non-limiting examples of oligomeric segments include polyalkylene oxide(e.g., polyethylene oxide), hydrogenated polybutadiene, hydrogenatedpolyisoprene, poly ((2,2-dimethyl)-1,3-propylene carbonate),polybutadiene, poly (diethylene glycol)adipate, poly (hexamethylenecarbonate), poly (ethylene-co-butylene), (diethylene glycol-orthophthalic anhydride) polyester, (1,6-hexanediol-ortho phthalic anhydride)polyester, (neopentyl glycol-ortho phthalic anhydride) polyester, apolysiloxane, and bisphenol A ethoxylate.

The term “oxycarbonyl bond,” as used herein, refers to a bond connectingan oxygen atom to a carbonyl group in an ester.

The term “polyalkylene,” when used herein in reference to a basepolymer, refers to a base polymer composed of linear or branchedalkylene repeating units having from 2 to 4 carbon atoms and/oroptionally a cyclic olefin of 3 to 10 carbon atoms (e.g., norbornene ortetracyclododecene). Each alkylene repeating unit is optionallysubstituted with one substituent selected from the group consisting ofchloro, methoxycarbonyl, ethoxycarbonyl, hydroxy, acetoxy, cyano, andphenyl. Polyalkylene base polymer can be a co-polymer (e.g., MABS, MMBS,MBS, SB, SAN, SMMA, COC, or COP copolymer). Non-limiting examples ofpolyalkylene base polymers include polystyrene, a cyclic olefin polymer(COP), a cyclic olefin copolymer (COC), MABS, SAN, SMMA, MBS, SB, andpolyacrylate (e.g., PMMA).

The term “polyethersulfone,” as used herein is meant a polymer of theformula:

This polymer is commercially available under the trade name Radel™ fromAmoco Corp.

The term “polyfluoroorgano group,” as used herein, refers to ahydrocarbon group, in which from two to fifty nine hydrogen atoms werereplaced with fluorine atoms. The polyfluoroorgano group contains one tothirty carbon atoms. The polyfluoroorgano group can contain linearalkyl, branched alkyl, or aryl groups, or any combination thereof. Thepolyfluoroorgano group can be a “polyfluoroacyl,” in which the carbonatom through which the polyfluoroorgano group (e.g., polyfluoroalkyl) isattached to the rest of the molecule, is substituted with oxo. The alkylchain within polyfluoroorgano group (e.g., polyfluoroalkyl) can beinterrupted by up to nine oxygen atoms, provided that two closest oxygenatoms within polyfluoroorgano are separated by at least two carbonatoms. When the polyfluoroorgano consists of a linear or branched alkyloptionally substituted with oxo and/or optionally interrupted withoxygen atoms, as defined herein, such group can be called apolyfluoroalkyl group. Some polyfluoroorgano groups (e.g.,polyfluoroalkyl) can have a theoretical molecular weight of from 100 Dato 1,500 Da. A polyfluoroalkyl can be CF₃(CF₂)_(r)(CH₂CH₂)_(p)—, where pis 0 or 1, r is from 2 to 20, or CF₃(CF₂)_(s)(CH₂CH₂O)_(X)—, where X isfrom 0 to 10, and s is from 1 to 20. Alternatively, polyfluoroalkyl canbe CH_(m)F_((3-m))(CF₂)_(r)CH₂CH₂— orCH_(m)F_((3-m))(CF₂)_(s)(CH₂CH₂O)_(X)—, where m is 0, 1, 2, or 3; X isfrom 0 to 10; r is an integer from 2 to 20; and s is an integer from 1to 20. In particular embodiments, X is 0. In other embodiments,polyfluoroalkyl is perfluoroheptanoyl. In certain embodiments,polyfluoroalkyl is formed from 1H,1H,2H,2H-perfluoro-1-decanol;1H,1H,2H,2H-perfluoro-1-octanol; 1H,1H,5H-perfluoro-1-pentanol; or1H,1H, perfluoro-1-butanol, and mixtures thereof. In still otherembodiments, polyfluoroalkyl is (CF₃)(CF₂)₅CH₂CH₂O—,(CF₃)(CF₂)₇CH₂CH₂O—, (CF₃)(CF₂)₅CH₂CH₂O—, CHF₂(CF₂)₃CH₂O—,(CF₃)(CF₂)₂CH₂O—, or (CF₃)(CF₂)₅—. In still other embodiments thepolyfluoroalkyl group contains (CF₃)(CF₂)₅—. In certain embodiments,polyfluoroorgano is —(O)_(q)—[C(═O)]_(r)—(CH₂)_(o)(CF₂)_(p)CF₃, in whichq is 0, and r is 1, or q is 1, and r is 0; o is from 0 to 2; and p isfrom 0 to 10.

By “poly(oxy-1,4-phenylenesulfonyl-1,4-phenyleneoxy-1,4-phenyleneisopropylidene-1,4-phenylene)” ismeant a polymer of the formula:

This polymer is commercially available under the trade name Udel™ P-3500from Solvay Advanced Polymers.

As used herein, the term “polysulfone” refers to a class of polymersthat include as a repeating subunit the moiety-aryl-SO₂-aryl.Polysulfones include, without limitation, polyethersulfones andpoly(oxy-1,4-phenylenesulfonyl-1,4-phenyleneoxy-1,4-phenyleneisopropylidene-1,4-phenylene).

By “surface active group” is meant a lipophilic group covalentlytethered to a surface-modifying macromolecule. The surface active groupcan be positioned to cap one, two, three, or four termini of the centralpolymeric portion of the surface-modifying macromolecule. Examples ofsurface active groups include, without limitation,polydimethylsiloxanes, hydrocarbons, polyfluoroorgano (e.g.,polyfluoroalkyl and fluorinated polyethers), and combinations thereof.

The term “surface modifying macromolecule,” as used herein, refers tothe macromolecules described herein (e.g., a compound according to anyone of formulas (I)-(IV), e.g., a compound of any one of compounds(1)-(9)).

The term “thermal degradation temperature,” as used herein, refers tothe lowest temperature at which there is an onset of weight loss of atleast 5% (w/w) of the surface-modifying macromolecule duringthermogravimetric analysis.

Other features and advantages of the invention will be apparent from theDrawings, Detailed Description, and the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A shows the structure of compound (1).

FIG. 1B shows the structure of compound (2).

FIG. 2A shows the structure of compound (3).

FIG. 2B shows the structure of compound (4).

FIG. 3A shows the structure of compound (5).

FIG. 3B shows the structure of compound (6).

FIG. 4 shows the structure of compound (7).

FIG. 5 shows the structure of compound (8).

FIG. 6 shows the structure of compound (9).

DETAILED DESCRIPTION

In general, the present invention provides surface-modifyingmacromolecules, the structure of which is based on linking an oligomericsegment to a surface active group through a linker having at least oneoxycarbonyl bond. The surface-modifying macromolecule of the inventioncan have a structure of any one of formulae (I)-(IV) described herein(e.g., the surface-modifying macromolecule of the invention can be anyone of compounds (1)-(9)).

In particular, the invention provides admixtures of base polymers withsurface modifying macromolecules and articles made therefrom. Thearticles of the invention can exhibit advantageous surface propertiesrelative to the articles lacking a surface-modifying macromolecule. Forexample, the surface properties can be modified to render such a surfaceresistant to biofouling, immobilization of biomolecules, or mediation ofbiomolecule denaturation. In particular, the surfaces of the inventioncan be resistant to fouling (e.g., biofouling). The surface of theinvention can also reduce degradation (e.g., through adsorption ordenaturation) of a biological agent (e.g., a polypeptide (e.g., amonoclonal antibody or an antigen-binding fragment thereof), apolynucleotide (e.g., siRNA or an antisense compound), or a vaccine);the degradation can be due to interactions between the biological agentand a surface lacking a surface-modifying macromolecule. Without beingbound by a theory, the inclusion of the surface-modifying macromoleculecan decrease the surface wetting (with water), thereby reducing thecontact between a biological agent (e.g., a protein, a nucleic acid, orbacteria) and the surface. The surface of the invention may be capableof sustaining a prolonged contact with a biologic without causingsubstantial denaturation or immobilization, e.g., the biologic can beabatacept, interferon β-1a, or insulin. In particular, these and otherbiologics may benefit from the surface properties of the invention, thesurface properties reducing or preventing undesired interactions betweenthe surface and the biologic (e.g., immobilization and/or denaturationof the biologic). Alternatively, the inclusion of the surface-modifyingmacromolecule can increase the surface wetting (with water). Suchmaterials may be useful in applications requiring a hydrophilic surface.

The desired surface properties in the articles of the invention arebelieved to be provided by surface-modifying macromolecules of theinvention that migrate during manufacturing to the surface of thearticle, thereby exposing the surface active groups at the surface ofthe article. The surface active groups are likely responsible, in part,for carrying the surface modifying macromolecule to the surface of theadmixture, where the surface active groups are exposed on the surface.The migration of the surface modifying macromolecules to the surface isa dynamic process and is dependent on the surface environment. Theprocess of migration is driven by the tendency towards establishing alow surface energy at the mixture's surface. When the balance betweenanchoring and surface migration is achieved, the surface-modifyingmacromolecule remains stable at the surface of the polymer, whilesimultaneously altering surface properties. Anchoring within the basepolymer can be provided by the oligomeric segment.

Aggregation of multiple oligomeric molecules can increase theireffective molecular radius, thereby lowering the permeability of theoligomeric molecules through a base polymer. Efficacy of the surfaceproperties modification can be improved by the surface-modifyingmacromolecules of the invention. By excluding the combinations ofhydrogen-bond donors and acceptors within the same molecule, the abilityof the surface-modifying macromolecules of the invention to migrate tothe surface of an article can be enhanced due to the likely reduction inaggregation. The surface-modifying macromolecules of the invention canexhibit enhanced ability to migrate to the surface of an article withoutcompromising their anchoring in a base polymer. Thus, certain of thesurface-modifying macromolecules of the invention do not containhydrogen bond donors (e.g., O—H, N—H, or S—H moieties). In particular,the surface-modifying macromolecules may be free of urethane moieties.

The selection of the combination of a particular surface modifyingmacromolecule (SMM) and a particular base polymer can be determined by anumber of factors. First, the type and amount of SMM to be added to basepolymer is determined in part by whether the admixture forms a singlestable phase, where the SMM is soluble in the base polymer (e.g.,separation of the admixture to form two or more distinct phases wouldindicate an unstable solution). Then, the compatibility of the admixturecan be tested by various known analytical methods. The surface of theadmixture as a film or as a fiber can be analyzed by any usefulspectroscopic method, such as X-ray photoelectron spectroscopy (XPS)with an elemental analysis (EA). Data from XPS could indicate the extentof modification of the surface by migrating SMMs and data from EA canindicate the extent of modification of the bulk material. Stableadmixtures can then be tested to determine the antifouling properties ofthe surface under various conditions.

The surface modification can maintain transparency of the neat basepolymer. Often the inclusion of admixtures in a base polymer can resultin diminished optical properties (e.g., lower transparency), therebylimiting the utility of such materials in applications, wheretransparency of the material is desirable. In contrast, the articles ofthe invention including a surface-modifying macromolecule and a basepolymer can have the transparency that is the same or slightly lowerthan that of the neat base polymer.

Articles of the invention can be prepared, at least in part, from a basepolymer using a process requiring a high temperature processing (e.g.,extrusion or molding). For example, COC and COP often require processingtemperatures of greater than 200° C. (e.g., greater than or equal to250° C. or greater than or equal to 300° C.). The surface-modifyingmacromolecules described herein can be thermally stable (e.g., can havea thermal degradation temperature of greater than or equal to 200° C.(e.g., greater than or equal to 250° C. or greater than or equal to 300°C.). Accordingly, articles of the invention can be formed from anadmixture of a base polymer and a surface-modifying macromolecule at atemperature of greater than 200° C. (e.g., greater than or equal to 250°C. or greater than or equal to 300° C.). Articles of the invention canbe manufactured (e.g., through high temperature processing, such as meltprocessing) from an admixture of a base polymer and a surface-modifyingmacromolecule. The surface-modifying macromolecule can be added prior tomelt processing of the base polymer to produce an article of theinvention. To form an admixture by melt processing, thesurface-modifying macromolecule can be, for example, mixed withpelletized or powdered polymer and then melt processed by known methodssuch as, for example, molding or melt extrusion. The surface-modifyingmacromolecule can be mixed directly with the polymer in the meltcondition or can first be pre-mixed with the polymer in the form of aconcentrate of the surface-modifying macromolecule/polymer admixture ina brabender mixer. If desired, an organic solution of thesurface-modifying macromolecule can be mixed with powdered or pelletizedbase polymer, followed by evaporation of the solvent and then by meltprocessing. Alternatively, the surface-modifying macromolecule can beinjected into a molten polymer stream to form an admixture immediatelyprior to extrusion into the desired shape.

After melt processing, an annealing step can be carried out to enhancethe development of advantageous properties described herein in the basepolymer. In addition to, or in lieu of, an annealing step, the meltprocessed combination can also be embossed between two heated rolls, oneor both of which can be patterned. An annealing step typically isconducted below the melt temperature of the polymer (e.g., at from about50° C. to about 220° C.).

The surface-modifying macromolecule is added to a base polymer inamounts sufficient to achieve the desired surface properties for aparticular application. Typically, the amount of surface-modifyingmacromolecule used is in the range of 0.05-15% (w/w) of the admixture.The amounts can be determined empirically and can be adjusted, asnecessary or desired, to achieve the desired surface properties withoutcompromising other physical properties of the base polymer.

Surface-Modifying Macromolecules

Surface-modifying macromolecules of the invention can be compounds ofany one of formulae (I), (I-A), (II), (II-A), (III), (III-A), (III-B),(III-C), and (IV).

The surface-modifying macromolecule of the invention can be a compoundof formula (I):

in which

each F_(T) is independently a surface active group selected from thegroup consisting of polydimethylsiloxanes, hydrocarbons,polyfluoroorgano, and combinations thereof;

X₁ is H, CH₃, or CH₂CH₃;

X₂ is H, CH₃, CH₂CH₃, or F_(T);

each of L₁ and L₂ is independently a bond, an oligomeric linker, or alinker with two terminal carbonyls; and

n is an integer from 5 to 50.

In particular, a compound of formula (I) can be a compound of formula(I-A):

in which each of m1 and m2 is independently an integer from 0 to 50(e.g., each of m1 and m2 is independently an integer from 1 to 50).

The surface-modifying macromolecule of the invention can be a compoundof formula (II):

in which

each F_(T) is independently a surface active group selected from thegroup consisting of polydimethylsiloxanes, hydrocarbons,polyfluoroorgano, and combinations thereof;

each of X₁ and X₂ is independently H, CH₃, CH₂CH₃, or F_(T);

each of L₁ and L₂ is independently a bond, an oligomeric linker, or alinker with two terminal carbonyls; and

each of n1 and n2 is independently an integer from 3 to 50.

In particular, the compound of formula (II) can be a compound of formula(II-A):

in which each of m1 and m2 is independently an integer from 0 to 50(e.g., each of m1 and m2 is independently an integer from 1 to 50).

The surface-modifying macromolecule of the invention can be a compoundof formula (III):G-(A)_(m)-[B-A]_(n)-B-G  (III)

in which

-   -   (i) A comprises polyurethane, polyurea, polyamide, polyalkylene        oxide, polycarbonate, polyester, polylactone, polysilicone,        polyethersulfone, polyalkylene, polyvinyl, polypeptide        polysaccharide, or an ether-linked or amine-linked segments        thereof (e.g., the segment in this case can refer to a repeating        unit in the listed oligomer);    -   (ii) B is a bond, an oligomeric linker, or a linker with two        terminal carbonyls; and    -   (iii) G is (a) a surface active group comprising a        polyfluoroorgano group or (b) H;    -   (iv) n is an integer from 1 to 10; and    -   (v) m is 0 or 1;    -   provided that at least one G is the surface active group        comprising a polyfluoroorgano group.

Oligomeric Segments

The surface-modifying macromolecules of the invention can be preparedfrom an oligomeric segment diol, triol, or tetraol. Because thereactions are moisture sensitive, they are typically carried out underan inert N₂ atmosphere and under anhydrous conditions. The resultingsurface-modifying macromolecules can be isolated and purified asappropriate. Surface modifying macromolecules of formula (I) or (II) canbe prepared, for example, from commercially availablemono-dihydroxysubstituted-alkyl or alkyloxyalkyl-terminated PEGs (e.g.,Ymer™ N120, a difunctional polyethylene glycol monomethyl ether, fromPerstorp). Exemplary oligomeric segment diols, triols, and tetraols areshown below.

Scheme 1 shows a non-limiting example of a structure of an oligomericsegment triol that can be used to prepare a surface-modifyingmacromolecule of formula (I) or (I-A).

Scheme 2 shows certain oligomeric segment tetraols that can be used inthe preparation of compounds according to formula (II) or (II-A).

Scheme 3 shows some of the oligomeric segment diols that can be used inthe preparation of compounds of formulas (III), (III-A), (III-B),(III-C), or (IV):

Diols known in the art can be used to prepare the compound of formula(Ill), (III-A), (III-B), (III-C), or (IV). For example, the diol of anoligomeric segment can be selected from the group consisting ofpolyurethane, polyurea, polyamide, polyalkylene oxide, polycarbonate,polyester, polylactone, polysilicone, polyethersulfone, polyalkylene,polyvinyl, polypeptide polysaccharide, or an ether-linked oramine-linked segments thereof (e.g., the segment in this case can referto a repeating unit in the listed oligomer).

Linkers

The compounds described herein (e.g., compounds according to any one offormulas (I)-(IV), e.g., compounds 1-7) can include linkers. The linkercomponent of the invention is, at its simplest, a bond between thealkoxy moiety and the surface active group segment (e.g., apolyfluoroorgano). Alternatively, the linker can be a linker having twoterminal carbonyl groups. The linker having two terminal carbonyl groupscan include a linear, cyclic, or branched molecular skeleton, optionallyhaving pendant groups. Yet another linker that can be used in thecompounds of the invention is an oligomeric linker. Oligomeric linkerscan contain from two to fifty bonded to each other identical chemicalmoieties. The chemical moiety in an oligomeric linker of the inventioncan be an alkylene oxide (e.g., —CH₂CH₂O—). Thus, the linker can be abond, an oligomeric linker, or a linker having two terminal carbonylgroups.

The linking of an oligomeric segment diol, triol, or tetraol to asurface active group segment (e.g., a polyfluoroorgano) can be achievedthrough a covalent bond forming reaction between the reactive groupspresent in the precursors of each segment (e.g., an oligomeric segment,a linker, or a surface active group). Examples of chemically reactivefunctional groups which may be employed for this purpose includehydroxyl and acyl halide. Thus, in a surface-modifying macromolecule ofthe invention, a surface active group segment (e.g., a polyfluoroorgano)can be linked to an oligomeric segment through one or more oxycarbonylbonds.

Spacer elements in the linker typically consist of linear or branchedchains and may include a C₁₋₁₀ alkyl, a heteroalkyl of 1 to 10 atoms, aC₂₋₁₀ alkenyl, a C₂₋₁₀ alkynyl, aryl of 5 to 10 atoms, or—(CH₂CH₂O)_(n)CH₂CH₂—, in which n is from 1 to 4.

Non-limiting examples of theoretical molecular weights that the linkersof the invention can have include from 100 Da to 2000 Da (e.g., from 100Da to 1500 Da, from 100 Da to 1000 Da, from 200 Da to 2000 Da, from 200Da to 1500 Da, from 200 Da to 1000 Da, from 300 Da to 2000 Da, from 300Da to 1500 Da, or from 300 Da to 1000 Da).

Medical Articles

The admixtures of the invention can be used to prepare medical articles,e.g., implantable medical articles. Certain medical articles of theinvention may require high temperature processing often exceeding 200°C. in the form of extruded or molded articles, where processingtemperatures can reach a range of 250-300° C. The admixtures of theinvention can have the required high temperature stability during theprocessing. The admixtures therefore can provide the required resistanceto degradation at high temperatures while providing the desiredbiocompatible properties, such as resistance to biofouling, resistanceto immobilization of biomolecules on the surface, and resistance tomediation of biomolecule denaturation. The technology can involve theincorporation of the SMMs into the base polymers which then bloom to thesurface, thus modifying the surface of the polymers but keeping the bulkproperties intact. The base polymers now have a fluorinated surface witha high degree of hydrophobicity. Articles that may be formed from theadmixtures of the invention include implanted medical devices which canbe percutaneous or cutaneous.

EXAMPLES

Abbreviations

YMer (Diol)=Hydroxy Terminated Polyethylene glycol monomethyl ether

YMerOH(Triol)=Trimethylolpropane Ethoxylate

XMer (Tetraol)=Pentaerythritol Ethoxylate

C25 (Diol)=Hydroxy Terminated Polidimethylsiloxane (EthyleneOxide-PDMS-Ethylene Oxide) block Copolymer

Preparation of Surface-Modifying Macromolecules

General Synthesis Description for Ester-based Surface-ModifyingMacromolecules

A diol such as Ymer diol, hydroxyl terminated polydimethylsiloxane, orpolyols such as trimethylolpropane ethoxylate or pentaerythritolethoxylate are reacted in a one-step reaction with a surface activegroup precursor (e.g., perfluoroheptanoyl chloride) at 40° C. in achlorinated organic solvent e.g. chloroform or methylene chloride in thepresence of an acid scavenger like pyridine or triethylamine for 24 h.This reaction end-caps the hydroxyl groups with polyfluoroorgano groups.Because the reactions are moisture sensitive, the reactions are carriedout under a nitrogen atmosphere using anhydrous solvents. After thereaction the solvent is rotary evaporated and the product is dissolvedin Tetrahydrofuran (THF) which dissolves the product and precipitatesthe pyridine salts which are filtered off and the filtrate rotaryevaporated further to dryness. The product is then purified bydissolving in minimum THF and precipitating in hexanes. This isperformed 3 times and after which the final product is again rotaryevaporated and finally dried in a vacuum oven at 60° C. overnight.

Synthesis of Compound 1

Glassware used for the synthesis was dried in an oven at 110° C.overnight. To a 2-necked 1000 mL oven dried round bottom flask equippedwith a stir bar was added 85 g (24 mmol) of C25-Diol (MW=3500). Theflask with the diol was degassed overnight at 60° C. with gentlestirring and then purged with dry N₂ the following day. The heating wasturned off. A 1000 mL graduated cylinder was charged with 320 mLanhydrous CHCl₃, sealed by a rubber septa and purged with dry N₂. TheCHCl₃ was transferred to the 2-necked flask via a cannula and the diolstirred vigorously to dissolve in the solvent. Anhydrous pyridine (11.53g, 146 mmol) was added to the C25-Diol solution using a plastic syringe,and the resulting mixture was stirred to dissolve all materials. Anotheroven dried 2-necked 1000 mL flask was charged with 32.51 g (85 mmol) ofperfluoroheptanoyl chloride. The flask was sealed with rubber septa anddegassed for 5 minutes, then purge with nitrogen. At this time 235 mL ofanhydrous CHCl₃ were added via cannula to the 1000 mL 2-necked flaskcontaining the perfluoroheptanoyl chloride. Stir at room temperature todissolve the acid chloride. This flask was fitted with an additionfunnel and the C25-Diol-pyridine solution in CHCl₃ was transferred via acannula into the addition funnel. N₂ flow through the reactor wasadjusted to a slow and steady rate. Continuous drop-wise addition ofC25-Diol-pyridine solution to the acid chloride solution was started atroom temperature and was continued over a period of ˜4 hours. Stirringwas maintained at a sufficient speed to achieve good mixing of reagents.After completing addition of the C25-Diol-pyridine solution, theaddition funnel was replaced with an air condenser, and the 2-neck flaskwas immerses in an oil bath placed on a heater fitted with athermocouple unit. The temperature was raised to 40° C., and thereaction continued at this temperature under N₂ for 24 h.

The product was purified by evaporating CHCl₃ in a rotary evaporator andby filtering the pyridine salts after addition of THF. The crude productwas then precipitated in isopropanol/hexanes mixture twice. The oil fromthe IPA/Hexane that precipitated was subjected to further washing withhot hexanes as follows. About 500 mL of Hexanes was added to the oil ina 1 L beaker with a stir bar. The mixture was stirred while the Hexaneswas heated to boiling. The heating was turned off, and the mixture wasallowed to cool for 5 minutes. The oil settles at the bottom at whichpoint the Hexane top layer is decanted. The isolated oil is furtherdissolved in THF, transferred to a round bottom flask and then thesolvents rotary evaporated. The oil is finally dried in a vacuum oven at40° C. for 24 h. The purified product (a mixture of di- andmono-substituted products) was characterized by GPC (Molecular Weightbased on Polystyrene Standards), elemental analysis for fluorine, ¹⁹FNMR, ¹H NMR, FTIR and TGA. Appearance: viscous oil. Weight Averagemolecular weight (polystyrene equivalent)=5791 g/mol. Polydispersity:2.85. Elemental analysis: F: 7.15% (theory: 10.53%). ¹⁹F NMR (CDCl₃, 400MHz): δ ppm −80.78 (m, CF₃), −118.43 (m, CF₂), −121.85 (m, CF₂), −122.62(m, CF₂), −126.14 (m, CF₂). ¹H NMR (CDCl₃, 400 MHz): δ ppm=0.0 (m,CH₃Si), 0.3 (br m, CH₂Si), 1.4 (br m, CH₂), 3.30 (m, CH₂'s), 4.30 (m,CH₂COO—). FTIR, neat (cm⁻¹): 3392 (OH), 2868 (CH₂), 1781 (O—C═O, ester),1241, 1212, 1141, 1087 (CF₃, CF₂,). Thermal decomposition temperature(TGA), N₂, at ca. 10% (w/w) loss=204° C.

Synthesis of Compound 2

Glassware used for the synthesis was dried in an oven at 110° C.overnight.

To a 2-necked 100 mL oven dried round bottom flask equipped with a stirbar was added 10 g (5 mmol) of PDMS C22—Diol (C22 diol, MW=3000). Theflask with the diol was degassed overnight at 60° C. with gentlestirring and then purged with dry N₂ the following day. Heating wasturned off. A 100 mL graduated cylinder was filled with 50 mL anhydrousCHCl₃, sealed with a rubber septum, and purged with dry N₂. The CHCl₃was transferred to the 2-necked flask via a cannula, and the diol wasstirred vigorously to dissolve in the solvent. Anhydrous pyridine (0.53g, 7 mmol) was then added to the C22-Diol solution using a plasticsyringe, and the resulting mixture was stirred to dissolve allmaterials. Another oven-dried 2-necked 250 mL flask was charged with3.19 g (8 mmol) perfluoroheptanoyl chloride. The flask was then sealedwith a rubber septum, and the mixture in the flask was degassed for 5minutes and purged with nitrogen. Then, 22 mL of anhydrous CHCl₃ wereadded using a graduated cylinder and a cannula to transfer the solventto the 250 mL 2-necked flask containing the perfluoroheptanoyl chloride.The resulting mixture was stirred at room temperature to dissolve theacid chloride. The flask was then equipped with an addition funnel, andthe C22 diol/pyridine solution in CHCl₃ was transferred to the additionfunnel using a cannula. N₂ flow through the reactor was adjusted to aslow and steady rate. C22 diol/pyridine solution was then addedcontinuously drop-wise to the acid chloride solution at room temperatureover a period of ˜4 hours. Stirring was maintained at a sufficient speedto achieve good mixing of reagents. After completing the addition of theC22 diol, the addition funnel was replaced with an air condenser, andthe 2-necked flask was immersed in an oil bath placed on a heater fittedwith a thermocouple unit. The temperature was raised to 50° C., and thereaction mixture was left at this temperature under N₂ for 24 h.

Then, heating and stirring were turned off. The flask was removed andits contents were poured into a round bottom flask. Volatiles wereremoved by rotary evaporation. Upon concentration, a dense precipitate(pyridine salts) formed. THF was added to dissolve the product, and theprecipitated pyridine salts were removed by filtration using a coarseWhatman Filter paper (No 4), as the pyridine salts are insoluble in THF.Volatiles were removed by rotary evaporation. The crude product was thendissolved in 100 mL of CHCl₃ and poured into a separatory funnel. 150 mLof water and 5 mL of 5N HCl were added to neutralize any remainingpyridine. The funnel was shaken, and the product was extracted intoCHCl₃. The bottom CHCl₃ layer containing product was then washed in aseparatory funnel sequentially with water, 5 mL of 5% (w/v) NaHCO₃solution to neutralize any remaining HCl, and with distilled water. TheCHCl₃ layer was separated and concentrated by rotary evaporation toobtain crude product, which was then dissolved in 10 ml of isopropanol.The resulting solution was added dropwise to a 1 L beaker containing 200mL of DI Water with 1% (v/v) MeOH with continuous stirring. The productseparated out as oil, at which time the solution was kept in an ice bathfor 20 minutes, and the top aqueous layer was decanted. The oil wasdissolved in THF and transferred into a 200 mL round bottom flask. Thevolatiles were removed by rotary evaporation at a maximum of 80° C. and4 mbar to remove residual solvents. The resulting product was dried in avacuum oven at 60° C. for 24 h to give a purified product as a lightyellow, clear oil (˜64% yield). The purified product was characterizedby GPC (Molecular Weight based on Polystyrene Standards), and elementalanalysis (for fluorine). Appearance: Light Yellow clear oil. WeightAverage Molecular Weight (Polystyrene equivalent) Mw=5589,Polydispersity PD=1.15. Elemental Analysis F: 12.86% (theory: 13.12%)

Synthesis of Compound 3

Glassware used for the synthesis was dried in an oven at 110° C.overnight. To a 2-necked 250 mL oven dried round bottom flask equippedwith a stir bar was added 20 g (8.0 mmol) of hydrogenated-hydroxylterminated polybutadiene (HLBH diol, MW=2000). The flask with the diolwas degassed overnight at 60° C. with gentle stirring and then purgedwith dry N₂ the following day. At this time, the heating was turned off.A 200 mL graduated cylinder was charged with 104 mL anhydrous CHCl₃,sealed by a rubber septa, and purged with dry N₂. The CHCl₃ wastransferred to the 2-necked flask via a cannula, and the diol wasstirred vigorously to dissolve in the solvent. At this time, anhydrouspyridine (3.82 g, 48 mmol) was added to the HLBH diol solution using aplastic syringe, and the resulting mixture was stirred to dissolve allmaterials. Another oven dried 2-necked 100 mL flask was charged withtrans-5-norbornene-2,3-dicarbonyl chloride (“NCl”; 3.70 g, 17 mmol),sealed with rubber septa, and degassed for 5 minutes, and then purgedwith nitrogen. At this time, 52 mL of anhydrous CHCl₃ were added using agraduated cylinder and a cannula to transfer the solvent to the 100 mL2-necked flask containing NCl. The resulting mixture was stirred todissolve NCl. The 250 mL 2-necked flask was then fitted with an additionfunnel, and the solution of NCl in CHCl₃ was transferred to the additionfunnel using a cannula. N₂ flow was adjusted through the reactor to aslow and steady rate. The solution of NCl was added continuouslydrop-wise to the HLBH-pyridine solution at room temperature over aperiod of ˜1 hour to form a pre-polymer. Stirring was maintained at asufficient speed to achieve good mixing of reagents.

In parallel, another oven-dried 50 mL flask was charged with Capstone™AI-62 perfluorinated reagent (5.45 g, 15 mmol). The flask was sealedwith rubber septa, degassed for 15 minutes, and purged with N₂.Anhydrous CHCl₃ (17 mL) and anhydrous pyridine (1.9 g, 24 mmol) wereadded. The mixture was stirred to dissolve all reagents. After theaddition of the NCl solution to the 250 mL 2-necked flask was complete,the Capstone™ AI-62 perfluorinated reagent solution was added to thisflask using a cannula with stirring. The addition funnel was replacedwith an air condenser, and the 250-mL 2-necked flask was immersed in anoil bath placed on a heater fitted with a thermocouple unit. Thetemperature was raised to 50° C., and the reaction continued at thistemperature under N₂ for 24 h.

After the reaction, heating and stirring were turned off. The reactionflask was removed, and its contents were poured into a round bottomflask. CHCl₃ was removed by rotary evaporation. Upon concentration, adense precipitate (pyridine salts) formed. THF was added to dissolve theproduct, and the precipitated pyridine salts were removed by filtrationusing a coarse Whatman Filter paper (No 4). Pyridine salts are insolublein THF. THF was removed by rotary evaporation. The crude product wasdissolved in 100 mL of CHCl₃ and was poured into a separatory funnel.100 mL of water were added, followed by the addition of 5 mL of (5N) HClto neutralize any remaining pyridine. The funnel was shaken, and theproduct was extracted into CHCl₃. The bottom CHCl₃ layer containingproduct was isolated and washed in a separatory funnel with water (5 mLof 5% NaHCO₃ solution were added to neutralize any remaining HCl). Theorganic layer was then washed once more with plain distilled water.Isolated CHCl₃ layer was concentrated by rotary evaporation to obtaincrude product. The crude product was dissolved in 10 mL of isopropanol(IPA) and was then added dropwise to a beaker containing 200 mL ofdeionized water containing 1% (v/v) MeOH with continuous stirring.Product separated out as an oil. The mixture was kept in ice bath for 20minutes, and the top water layer was decanted. The oil was dissolved inTHF and transferred into 200 mL round bottom flask. THF was removed byrotary evaporation at a maximum temperature of 80° C. and 4 mbar toremove all residual solvents. The resulting product was dried in avacuum oven at 60° C. for 24 h to give a purified product as a viscousoil (˜55% yield). The purified product (a mixture of di- andmono-substituted products) was characterized by GPC, elemental analysis,for fluorine, and Hi-Res TGA. Appearance: light yellow viscous liquid.Weight Average molecular weight (polystyrene equivalent)=12389 g/mol.Polydispersity, PD: 1.43. Elemental analysis: F: 10.6% (theory: 14.08%).Thermal decomposition temperature (TGA), N₂, at 10% (w/w) loss: 363° C.

Synthesis of Compound 4

Compound 4 was prepared according to a procedure similar to compound 3.

Glassware used for the synthesis was dried in an oven at 110° C.overnight. To a 2-necked 250 mL oven dried round bottom flask equippedwith a stir bar was added 15 g (6.0 mmol) of hydrogenated-hydroxylterminated polybutadiene (HLBH diol, MW=2000). The flask with the diolwas degassed overnight at 60° C. with gentle stirring and then purgedwith dry N₂ the following day. At this time, the heating was turned off.A 100 mL graduated cylinder was charged with 12 mL anhydrous CHCl₃,sealed by a rubber septa, and purged with dry N₂. The CHCl₃ wastransferred to the 2-necked flask via a cannula, and the diol wasstirred vigorously to dissolve in the solvent. At this time, anhydrouspyridine (0.95 g, 12 mmol) was added to the HLBH diol solution using aplastic syringe, and the resulting mixture was stirred to dissolve allmaterials. Another oven dried 2-necked 100 mL flask was charged withterephthaloyl chloride (2.57 g, 13 mmol), sealed with rubber septa, anddegassed for 5 minutes, and then purged with nitrogen. At this time, 85mL of anhydrous CHCl₃ were added using a graduated cylinder and acannula to transfer the solvent to the 100 mL 2-necked flask. Theresulting mixture was stirred to dissolve terephthaloyl chloride. The250 mL 2-necked flask was then fitted with an addition funnel, and thesolution of terephthaloyl chloride in CHCl₃ was transferred to theaddition funnel using a cannula. N₂ flow was adjusted through thereactor to a slow and steady rate. The solution of terephthaloylchloride was added continuously drop-wise to the HLBH-pyridine solutionat room temperature over a period of ˜1 hour to form a pre-polymer.Stirring was maintained at a sufficient speed to achieve good mixing ofreagents.

In parallel, another oven-dried 50 mL flask was charged with Capstone™AI-62 perfluorinated reagent (5.45 g, 15 mmol). The flask was sealedwith rubber septa, degassed for 15 minutes, and purged with N₂.Anhydrous CHCl₃ (12 mL) and anhydrous pyridine (0.95 g, 12 mmol) wereadded. The mixture was stirred to dissolve all reagents. After theaddition of the terephthaloyl chloride solution to the 250 mL 2-neckedflask was complete, the Capstone™ AI-62 perfluorinated reagent solutionwas added to this flask with stirring. The addition funnel was replacedwith an air condenser, and the 250-mL 2-necked flask was immersed in anoil bath placed on a heater fitted with a thermocouple unit. Thetemperature was raised to 50° C., and the reaction continued at thistemperature under N₂ for 24 h.

After the reaction, heating and stirring were turned off. The reactionflask was removed, and its contents were poured into a round bottomflask. CHCl₃ was removed by rotary evaporation. Upon concentration, adense precipitate (pyridine salts) formed. THF was added to dissolve theproduct, and the precipitated pyridine salts were removed by filtrationusing a coarse Whatman Filter paper (No 4). Pyridine salts are insolublein THF. THF was removed by rotary evaporation. The crude product wasdissolved in 100 mL of CHCl₃ and was poured into a separatory funnel.100 mL of water were added, followed by the addition of 5 mL of (5N) HClto neutralize any remaining pyridine. The funnel was shaken, and theproduct was extracted into CHCl₃. The bottom CHCl₃ layer containingproduct was isolated and washed in a separatory funnel with water (5 mLof 5% NaHCO₃ solution were added to neutralize any remaining HCl). Theorganic layer was then washed once more with plain distilled water.Isolated CHCl₃ layer was concentrated by rotary evaporation to obtaincrude product. The crude product was dissolved in 10 mL of isopropanol(IPA) and was then added dropwise to a beaker containing 200 mL ofdeionized water containing 1% (v/v) MeOH with continuous stirring.Product separated out as an oil. The mixture was kept in ice bath for 20minutes, and the top water layer was decanted. The oil was dissolved inTHF and transferred into 200 mL round bottom flask. THF was removed byrotary evaporation at a maximum temperature of 80° C. and 4 mbar toremove all residual solvents. The resulting product was dried in avacuum oven at 60° C. for 24 h to give a purified product as a viscousoil (˜87% yield). The purified product (a mixture of di- andmono-substituted products) was characterized by GPC, elemental analysis,for fluorine, and Hi-Res TGA. Appearance: off-white viscous liquid.Weight Average molecular weight (polystyrene equivalent)=10757 g/mol.Polydispersity, PD: 1.33. Elemental analysis: F: 11.29% (theory:14.21%). Thermal decomposition temperature (TGA), N₂, at 10% (w/w) loss:354° C.

Synthesis of Compound 5

Glassware used for the synthesis was dried in an oven at 110° C.overnight. To a 2-necked 100 mL oven dried round bottom flask equippedwith a stir bar was added 10 g (5 mmol) of hydrogenated-hydroxylterminated polyisoprene (HHTPI diol, MW=2000). The flask with the diolwas degassed overnight at 60° C. with gentle stirring and then purgedwith dry N₂ the following day. At this time, the heating was turned off.A 100 mL graduated cylinder was charged with 50 mL anhydrous CHCl₃,sealed by a rubber septa, and purged with dry N₂. The CHCl₃ wastransferred to the 2-necked flask via a cannula, and the diol wasstirred vigorously to dissolve in the solvent. At this time, excessanhydrous pyridine (0.75 g, 9 mmol) was added to the HHTPI diol solutionusing a plastic syringe, and the resulting mixture was stirred todissolve all materials. Another oven dried 2-necked 250 mL flask wascharged with perfluoroheptanoyl chloride (4.51 g, 12 mmol), sealed withrubber septa, and degassed for 5 minutes, and then purged with nitrogen.At this time, 22 mL of anhydrous CHCl₃ was added using a graduatedcylinder and a cannula to transfer the solvent to the 250 mL 2-neckedflask containing the perfluoroheptanoyl chloride. The resulting mixturewas stirred at room temperature to dissolve the acid chloride. Anaddition funnel was fitted to this flask, and the HHTPI-pyridinesolution in CHCl₃ was added into the addition funnel. N₂ flow wasadjusted through the reactor to a slow and steady rate. HLBH-Pyridinesolution was added continuously drop-wise to the acid chloride solutionat room temperature over a period of ˜4 hours. Stirring was maintainedat a sufficient speed to achieve good mixing of reagents. Aftercompleting addition of the HHTPI diol, the addition funnel was replacedwith an air condenser, and the 2-necked flask was immersed in an oilbath on a heater fitted with a thermocouple unit. The temperature wasraised to 50° C., and the reaction continued at this temperature underN₂ for 24 h.

After the reaction, heating and stirring were turned off. The reactionflask was removed, and its contents were poured into a round bottomflask. CHCl₃ was removed by rotary evaporation. Upon concentration, adense precipitate (pyridine salts) formed. THF was added to dissolve theproduct, and the precipitated pyridine salts were removed by filtrationusing a coarse Whatman Filter paper (No 4). Pyridine salts are insolublein THF. THF was removed by rotary evaporation. The crude product wasdissolved in 100 mL of CHCl₃ and was poured into a separatory funnel.150 mL of water were added, followed by the addition of 5 mL of (5N) HClto neutralize any remaining pyridine. The funnel was shaken, and theproduct was extracted into CHCl₃. The bottom CHCl₃ layer containingproduct was isolated and washed in separatory funnel with water (5 mL of5% NaHCO₃ solution were added to neutralize any remaining HCl). Theorganic layer was then washed once more with plain distilled water.Isolated CHCl₃ layer was concentrated by rotary evaporation to obtaincrude product. The crude product was dissolved in 10 mL of isopropanol(IPA) and was added dropwise to a 1 L beaker containing 200 mL ofdeionized water containing 1% (v/v) MeOH with continuous stirring.Product separated out as an oil. The mixture was kept in ice bath for 20minutes, and the top water layer was decanted. The oil was dissolved inTHF and transferred into 200 mL round bottom flask. THF was removed byrotary evaporation at a maximum temperature of 80° C. and 4 mbar toremove all residual solvents. The resulting product was dried in avacuum oven at 60° C. for 24 h to give a purified product as a colorlessviscous oil (˜99.9% yield). The purified product (a mixture of di- andmono-substituted products) was characterized by GPC, elemental analysis,for fluorine, and Hi-Res TGA. Appearance: colorless viscous liquid.Weight Average molecular weight (polystyrene equivalent)=12622 g/mol.Polydispersity, PD: 1.53. Elemental analysis: F: 13.50% (theory:17.13%). Thermal decomposition temperature (TGA), N₂, at 5% (w/w) loss:260° C.

Synthesis of Compound 6

Glassware used for the synthesis was dried in an oven at 110° C.overnight. To a 2-necked 1000 mL oven dried round bottom flask equippedwith a stir bar was added 100 g (40 mmol) of Hydrogenated-hydroxylterminated polybutadiene (HLBH diol, MW=2000). The flask with the diolwas degassed overnight at 60° C. with gentle stirring and then purgedwith dry N₂ the following day. At this time, the heating was turned off.A 1000 mL graduated cylinder was charged with 415 mL anhydrous CHCl₃,sealed by a rubber septa, and purged with dry N₂. The CHCl₃ wastransferred to the 2-necked flask via a cannula, and the diol wasstirred vigorously to dissolve in the solvent. Now excess anhydrouspyridine (19.08 g, 241 mmol) was added to the HLBH diol solution using aplastic syringe, and the resulting mixture was stirred to dissolve allmaterials. Another oven dried 2-necked 1000 mL flask was charged with38.45 g, (101 mmol) perfluoroheptanoyl chloride, sealed with rubbersepta, and degassed for 5 minutes, and then purged with nitrogen. Atthis time, 277 mL of anhydrous CHCl₃ was added using a graduatedcylinder and a cannula to transfer the solvent to the 1000 mL 2-neckedflask containing the perfluoroheptanoyl chloride. The resulting mixturewas stirred at room temperature to dissolve the acid chloride. Anaddition funnel was fitted to this flask, and the HLBH-pyridine solutionin CHCL₃ was added into the addition funnel using a cannula. N₂ flow wasadjusted through the reactor to a slow and steady rate. Continuousdrop-wise addition of HLBH-Pyridine solution to the acid chloridesolution was started at room temperature over a period of ˜4 hours.Stirring was maintained at a sufficient speed to achieve good mixing ofreagents. After completing addition of the HLBH, the addition funnel wasreplaced with an air condenser, and the 2-necked flask was immersed inan oil bath on a heater fitted with a thermocouple unit. The temperaturewas raised to 50° C., and the reaction continued at this temperatureunder N₂ for 24 h.

After the reaction, heating and stirring were turned off. The reactionflask was removed, and its contents were poured into a round bottomflask. CHCl₃ was removed by rotary evaporation. Upon concentration, adense precipitate (pyridine salts) formed. THF was added to dissolve theproduct, and the precipitated pyridine salts were removed by filtrationusing a coarse Whatman Filter paper (No 4). Pyridine salts are insolublein THF. THF was removed by rotary evaporation. The crude product wasdissolved in 400 mL of CHCl₃ and was poured into a separatory funnel.500 mL of water were added, followed by the addition of 20 mL of (5N)HCl to neutralize any remaining pyridine. The funnel was shaken, and theproduct was extracted into CHCl₃. The bottom CHCl₃ layer containingproduct was isolated, and washed in a separatory funnel with water (20mL of 5% NaHCO₃ solution were added to neutralize any remaining HCl).The organic layer was then washed once more with plain distilled water.Isolated CHCl₃ layer was concentrated by rotary evaporation to obtaincrude product. The crude product was dissolved in 20 mL of THF and wasthen added dropwise to a 4 L beaker containing 1200 mL of deionizedwater containing 1% (v/v) MeOH with continuous stirring. Productseparated out as an oil. The mixture was kept in ice bath for 20minutes, and the top hexane layer was decanted. The oil was dissolved inTHF and transferred into 500 mL round bottom flask. THF was removed byrotary evaporation at a maximum temperature of 80° C. and 4 mbar toremove all residual solvents. The resulting product was dried in avacuum oven at 60° C. for 24 h to give a purified product as a yellowviscous oil (˜80% yield). The purified product (a mixture of di- andmono-substituted products) was characterized by GPC, elemental analysisfor fluorine and Hi-Res TGA. Appearance: light yellow viscous liquid.Weight Average molecular weight (polystyrene equivalent)=6099 g/mol.Polydispersity, PD: 1.08. Elemental analysis: F: 12.84% (theory:15.54%). Thermal decomposition temperature (TGA), N₂, at 5% (w/w) loss:343° C.

Synthesis of Compound 7

Glassware used for the synthesis was dried in an oven at 110° C.overnight. To a 2-necked 1000 mL oven dried round bottom flask equippedwith a stir bar was added 65 g (63 mmol) of YMer-diol (MW=1000). Theflask with the diol was degassed overnight at 60° C. with gentlestirring and then purged with dry N₂ the following day. At this time,heating was turned off. A 1000 mL graduated cylinder was charged with374 mL anhydrous CHCl₃, sealed by rubber septa, and purged with dry N₂.The CHCl₃ was transferred to the 2-necked flask via a cannula, and thediol was stirred vigorously to dissolve in the solvent. Excess anhydrouspyridine (30 g, 375 mmol) was added to the YMer-diol solution using aplastic syringe, the resulting stir to dissolve all materials. Anotheroven dried 2-necked 1000 mL flask was charged with 59.82 g (156 mmol) ofperfluoroheptanoyl chloride, sealed with rubber septa, and degassed for5 minutes, then purged with nitrogen. At this time 250 mL of anhydrousCHCl₃ were added using a graduated cylinder and cannula to transfer thesolvent to the 1000 mL 2-necked flask containing the perfluoroheptanoylchloride. The resulting mixture was stirred at room temperature todissolve the acid chloride. An addition funnel was fitted to this flaskand using a cannula transfer the YMer-diol-pyridine solution in CHCl₃into the addition funnel. N₂ flow through the reactor was adjusted to aslow and steady rate. YMer-diol-pyridine solution was added drop-wise,continuously to the acid chloride solution at room temperature over aperiod of ˜4 hours. Stirring was maintained at a sufficient speed toachieve good mixing of reagents. After completing the addition of theYMer-diol-pyridine solution, the addition funnel was replaced with anair condenser, and the 2-necked flask was immersed in an oil bath placedon a heater fitted with a thermocouple unit. The temperature was raisedto 40° C., and the reaction continued at this temperature under N₂ for24 h.

After the reaction, heating and stirring were turned off. The reactionflask was removed, and the contents were poured into a round bottomflask. CHCl₃ was removed by rotary evaporation. Upon concentration, adense precipitate (pyridine salts) formed. THF was added to dissolve theproduct. The flask was cooled in an ice bath for 20 minutes, at whichtime, the precipitated pyridine salts were removed by gravity filtrationusing a coarse Whatman Filter paper (No 4). Pyridine salts are insolublein THF. THF was removed by rotary evaporation. The resulting crudeproduct was dissolved in a minimum quantity of Isopropanol (IPA), andthis solution was added to 700 mL of hexanes in a beaker with a stirbar. An oil separated out. The top layer was decanted and washed oncewith 200 mL of hexanes. The residue was then dissolved in 200 mL of THFand transferred to a 500 mL round bottom flask. Rotary evaporation ofthe solvents at a maximum temperature of 75° C. and 4 mbar vacuumfurnished an oil, which was then transferred to a wide mouth jar andfurther dried for 24 h at 60° C. under vacuum to yield the pure productwhich solidifies upon cooling at room temperature to an off white waxysemi-solid (Yield 82%). The purified product was characterized by GPC(Molecular Weight based on Polystyrene Standards), elemental analysisfor fluorine, ¹⁹F NMR, ¹H NMR, FTIR and TGA. Appearance: waxysemi-solid. Weight Average molecular weight (polystyreneequivalent)=2498 g/mol. Polydispersity: 1.04. Elemental Analysis: F:27.79% (theory: 28.54%). ¹⁹F NMR (CDCl₃, 400 MHz): δ ppm −81.3 (m, CF₃),−118.88 (m, CF₂), −122.37 (m, CF₂), −123.28 (m, CF₂), −126 (m, CF₂). ¹HNMR (CDCl₃, 400 MHz): δ ppm 0.83 (t, CH₃CH₂), 1.44 (q, CH₂CH₃), 3.34 (m,CH₂), 3.51 (m, CH₂), 3.54 (m, CH₂), 4.30 (m, CH₂COO—). FTIR, neat(cm⁻¹): 2882 (CH2), 1783 (O—C═O, ester), 1235, 1203, 1143, 1104 (CF₃,CF₂). Thermal decomposition temperature (TGA), N₂, at ca. 10% (w/w)loss=352° C.

Synthesis of Compound 8

Compound 8 was prepared according to a procedure similar to that usedfor the preparation of compound 7.

Glassware used for the synthesis was dried in an oven at 110° C.overnight. To a 2-necked 1000 mL oven dried round bottom flask equippedwith a stir bar was added 60 g (59 mmol) of YMerOH-triol (MW=1014). Theflask with the triol was degassed overnight at 60° C. with gentlestirring and then purged with dry N₂ the following day. Heating wasturned off. A 1000 mL graduated cylinder was charged with 435 mLanhydrous CHCl₃, sealed with rubber septa, and purged with dry N₂. TheCHCl₃ liquid was transferred to the 2-necked flask via a cannula, andthe triol was stirred vigorously to dissolve in the solvent. Excessanhydrous pyridine (37 g, 473 mmol) was added to the YMer-triol solutionusing a plastic syringe, the resulting mixture was stirred to dissolveall materials. Another oven dried 2-necked 1000 mL flask was chargedwith 84.88 g (222 mmol) of perfluoroheptanoyl chloride, sealed withrubber septa, and degassed for 5 minutes, then purged with nitrogen. 290mL of anhydrous CHCl₃ were added using a graduated cylinder and cannulato transfer the solvent to the 1000 mL 2-necked flask containing theperfluoroheptanoyl chloride. The mixture was stirred at room temperatureto dissolve the acid chloride. An addition funnel was fitted to thisflask, and the YMerOH-triol-pyridine solution in CHCL₃ was transferredto the addition funnel using a cannula. N₂ flow through the reactor wasadjusted to a slow and steady rate. YMerOH-triol-pyridine solution wasadded continuously drop-wise to the acid chloride solution at roomtemperature over a period of ˜4 hours. Stirring was maintained at asufficient speed to achieve good mixing of reagents. After completingthe addition of the YMer-triol-pyridine solution, the addition funnelwas replaced with an air condenser, and the 2-necked flask was immersedin an oil bath placed on a heater fitted with a thermocouple unit. Thetemperature was raised to 40° C., and the reaction was continued at thistemperature under N₂ for 24 h.

The resulting product was purified in a similar manner to compound 7described above. The purification involved rotary evaporation of CHCl₃,addition of THF, and separation of the pyridine salts by filtration. Theproduct was then precipated in isopropanol (IPA)/Hexanes, washed asdescribed above for compound 7, and dried at 75° C. and 4 mbar. Finaldrying was also done under vacuum at 60° C. for 24 h to yield an oil(Yield 78.2%). The purified product was characterized by GPC (MolecularWeight based on Polystyrene Standards), elemental analysis for fluorine,¹⁹F NMR, ¹H NMR, FTIR, and TGA. Appearance: light yellow, viscous oil.Weight Average molecular weight (polystyrene equivalent)=2321 g/mol.Polydispersity: 1.06. Elemental Analysis: F: 35.13% (theory: 36.11%).¹⁹F NMR (CDCl₃, 400 MHz): δ ppm −81.30 (m, CF₃), −118.90 (m, CF₂),−122.27 (m, CF₂), −123.07 (m, CF₂), −126.62 (m, CF₂). ¹H NMR (CDCl₃, 400MHz): δ ppm 0.83 (t, CH₃CH₂), 1.44 (q, CH₂CH₃), 3.34 (m, CH₂O), 3.41 (m,CH₂'s), 3.74 (m, CH₂), 4.30 (m, CH₂COO—). FTIR, neat (cm⁻¹): 2870 (CH₂),1780 (O—C═O, ester), 1235, 1202, 1141, 1103 (CF₃, CF₂). Thermaldecomposition temperature (TGA), N₂, at ca. 10% (w/w) loss=333° C.

Synthesis of Compound 9

Compound 9 was prepared according to a procedure similar to that usedfor the preparation of compound 7.

Glassware used for the synthesis was dried in an oven at 110° C.overnight. To a 2-necked 1000 mL oven dried round bottom flask equippedwith a stir bar was added 50 g (65 mmol) of XMer-Tetraol (MW=771). Theflask with the tetraol was degassed overnight at 60° C. with gentlestirring and then purged with dry N₂ the following day. Heating wasturned off. A 1000 mL graduated cylinder was charged with 400 mLanhydrous CHCl₃, sealed with rubber septa, and purged with dry N₂. CHCl₃was transferred to the 2-necked flask via a cannula, and the tetraol wasstirred vigorously to dissolve in the solvent. Excess anhydrous pyridine(51.30 g, 649 mmol) was added to the XMer-Tetraol solution using aplastic syringe, and the resulting mixture was stirred to dissolve allmaterials. Another oven dried 2-necked 1000 mL flask was charged with111.63 g (292 mmol) of perfluoroheptanoyl chloride, sealed with rubbersepta, and degassed for 5 minutes, and then purged with nitrogen. 300 mLof anhydrous CHCl₃ were added using a graduated cylinder and cannula totransfer the solvent to the 1000 mL 2-necked flask containingperfluoroheptanoyl chloride. The resulting mixture was stirred at roomtemperature to dissolve the acid chloride. An addition funnel wasattached to this flask, and the XMer-tetraol-pyridine solution in CHCL₃was transferred into the addition funnel via a cannula. N₂ flow throughthe reactor was adjusted to a slow and steady rate.XMer-tetraol-pyridine solution was added continuously drop-wise to theacid chloride solution at room temperature over a period of ˜4 hours.Stirring was maintained at a sufficient speed to achieve good mixing ofreagents. After completing addition of the XMer-tetraol-pyridinesolution, the addition funnel was replaced with an air condenser, andthe 2-necked flask was immersed in an oil bath placed on a heater fittedwith a thermocouple unit. The temperature was raised to 40° C., and thereaction continued at this temperature under N₂ for 24 h.

The resulting product was purified in a similar manner to compound 7described above, where the CHCl₃ was removed by rotary evaporation,addition of THF, and the separation of pyridine salts by filtrationafter adding THF. The product was then precipitated in isopropanol(IPA)/hexanes, washed as described for compound 7, and dried at 75° C.and 4 mbar. Final drying was also done under vacuum at 60° C. for 24 hto yield an oil (Yield 80.9%). The purified product was characterized byGPC (Molecular Weight based on Polystyrene Standards), elementalanalysis for fluorine, ¹⁹F NMR, ¹H NMR, FTIR, and TGA. Appearance: lightyellow, viscous oil. Weight Average molecular weight (polystyreneequivalent)=2410 g/mol. Polydispersity: 1.04. Elemental Analysis: F:44.07% (theory: 45.85%). ¹⁹F NMR (CDCl₃, 400 MHz): δ ppm −81.37 (m,CF₃), −118.89 (m, CF₂), −122.27 (m, CF₂), −123.06 (m, CF₂), −26.64 (m,CF₂). ¹H NMR (CDCl₃, 400 MHz): δ ppm 3.36 (m, CH₂'s), 3.75 (m, CH₂O),4.39 (m, CH₂O), 4.49 (m, CH₂COO—). FTIR, neat (cm⁻¹): 2870 (CH₂), 1780(O—C═O, ester), 1235, 1202, 1141, 1103 (CF₃, CF₂). Thermal decompositiontemperature (TGA), N₂, at ca. 10% (w/w) loss=327° C.

Compounding

Compounds of the invention can be used to form an admixture with a basepolymer (e.g., COP, such as Zeonex® 690R, or COC, such as TOPAS® (e.g.,COC 8007S or COC 6013S)) as described herein for compound 6.

Compound 6 was compounded with COP resin Zeonex® 690R, TOPAS® COC 8007Sor 6013S in 15 mL DSM Xplore twin screw microcompounder in a batch modeto extrude rods. Compounding was performed by filling at 75 rpm andprocessing at 100 rpm at 250° C., 280° C., or 300° C. under N₂. Theprocessing of COC 8007S was performed at 250° C. The processing of COC6013S was performed at 300° C. The cycle time was 3 minutes.

Resulting rods were analyzed visually for clarity and by XPS analysisfor surface modification (% F). Elemental analysis was used to determineactual concentration of the surface-modifying macromolecule in resin andto compare the analysis results to the theoretical target concentration.

Table 1 shows the results of the XPS elemental composition analysis ofthe surface of the rods prepared from an admixture of Zeonex® 690R with0.5% (w/w) of compound 6.

TABLE 1 Element n = 1 n = 2 n = 3 Average SD C1s 91.21 89.34 89.83 90.130.97 F1s 7.37 8.48 8.21 8.02 0.58 N1s 0 0 0 0.00 0.00 O1s 1.43 2.18 1.961.86 0.39 Si2p 0 0 0 0.00 0.00

Table 2 shows the results of the XPS analysis of COC-8007S rods withsurface-modifying macromolecules of the invention at variousconcentrations (noted as a (w/w) percentage) (n=2).

TABLE 2 Formulation % F (Average) SD  0.5% (w/w) compound 6 5.41 0.83  1% (w/w) compound 6 8.76 0.98  0.5% (w/w) compound 3 5.12 0.26   1%(w/w) compound 3 5.79 1.45  0.5% (w/w) compound 4 6.15 0.57   1% (w/w)compound 4 5.25 0.01  0.5% (w/w) compound 5 9.38 1.01   1% (w/w)compound 5 8.98 0.53 0.75% (w/w) compound 7 19.74 1.09

A comparison of the target concentration to the actual concentration ofthe surface-modifying macromolecules in COC 8007S rods is provided inTable 3.

TABLE 3 Formulation Target Conc (%) Actual Conc (%)  0.5% (w/w) compound6 0.5 0.4   1% (w/w) compound 6 1 0.9  0.5% (w/w) compound 3 0.5 0.4  1% (w/w) compound 3 1 0.72  0.5% (w/w) compound 4 0.5 0.6   1% (w/w)compound 4 1 0.64  0.5% (w/w) compound 5 0.5 0.4   1% (w/w) compound 5 10.8 0.75% (w/w) compound 7 0.75 0.44

Table 4 shows the results of the XPS analysis of COC-6013S rods withsurface-modifying macromolecules of the invention at variousconcentration (noted as a (w/w) percentage) (n=2).

TABLE 4 Formulation % F (Average) SD 0.5% (w/w) compound 6 5.94 2.20  1% (w/w) compound 6 6.29 0.92   2% (w/w) compound 6 9.72 1.14 0.5%(w/w) compound 4 4.29 0.76   1% (w/w) compound 4 5.90 0.21 0.5% (w/w)compound 3 3.99 0.53

Table 5 shows a comparison of the target to actual concentration of thesurface-modifying macromolecules in COC 6013S rods.

TABLE 5 Formulation Target Conc. (%) Actual Conc. (%) 0.5% (w/w)compound 6 0.5 0.8   1% (w/w) compound 6 1 0.84   2% (w/w) compound 6 21 0.5% (w/w) compound 4 0.5 0.41   1% (w/w) compound 4 1 0.74 0.5% (w/w)compound 3 0.5 0.5

Measurement of Immobilization and/or Denaturation of a Biologic on theSurface

The capability of the surface of an article of the invention reducing orpreventing immobilization of a biologic can be compared to that of thesurface of an article made from the same base polymer but lacking asurface-modifying macromolecule. In a non-limiting example, a vesselprepared from an admixture of a base polymer and a surface-modifyingmacromolecule (“Vessel) can be charged with a solution (e.g., aqueoussolution) of a biologic (e.g., interferon β, a monoclonal antibody, afusion protein (e.g., abatacept), an siRNA, or DNA (e.g., plasmid)) ofpredetermined concentration. Vessel can then be sealed, e.g., underinert atmosphere (e.g., under Ar or N₂). After storage of the biologicsolution inside sealed Vessel for a period of time (e.g., 1 day, 3 days,1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 0.5 years, 0.75years, 1 year, etc) at room temperature or at a lower temperature (e.g.,at 4° C. or at 0° C.) under ambient light (e.g., fluorescent light) orin the dark, the solution stored inside Vessel can be assessed for thetotal protein or nucleic acid concentration (e.g., using UV-Visspectrometry or particle analyzer as known in the art). The change inthe concentration of the biologic over time inside Vessel can then becompared to the change in the concentration of the biologic over timeinside a vessel lacking a surface-modifying macromolecule (“ControlVessel”). The magnitude of the decrease of the biologic concentration inVessel can be at least 5% lower (e.g., at least 10% lower, at least 20%lower, at least 30% lower, at least 40% lower, or at least 50% lower)than that of the biologic concentration in Control Vessel over the sameperiod of time, provided that the solutions were stored at the sametemperature and light conditions.

Other Embodiments

Various modifications and variations of the described materials andmethods of use of the invention will be apparent to those skilled in theart without departing from the scope and spirit of the invention.Although the invention has been described in connection with specificembodiments, it should be understood that the invention as claimedshould not be unduly limited to such specific embodiments. Indeed,various modifications of the described modes for carrying out theinvention that are obvious to those skilled in the art are intended tobe within the scope of the invention.

Other embodiments are in the claims.

What is claimed is:
 1. A compound of formula (I):

wherein each F_(T) is independently a surface active group selected fromthe group consisting of polydimethylsiloxanes, hydrocarbons,polyfluoroorgano, and combinations thereof; X₁ is H, CH₃, or CH₂CH₃;each of X₂ and X₃ is independently H, CH₃, CH₂CH₃, or F_(T); each of L₁and L₂ is independently a bond, an oligomeric linker, or a linker withtwo terminal carbonyls; and n is an integer from 5 to
 50. 2. Thecompound of claim 1, wherein each of L₁ and L₂ is a bond.
 3. Thecompound of claim 1, wherein each of L₁ and L₂ is a linker with twoterminal carbonyls.
 4. The compound of claim 1, wherein each of L₁ andL₂ is an oligomeric linker.
 5. The compound of claim 4, wherein saidoligomeric linker comprises (alkylene oxide)_(z), wherein z is aninteger from 2 to
 20. 6. The compound of claim 5, wherein saidoligomeric linker comprises (ethylene oxide)_(z), wherein z is aninteger from 2 to
 20. 7. The compound of claim 1 having a structure offormula (I-A):

wherein each of m1 and m2 is independently an integer from 0 to
 50. 8.The compound of claim 7, wherein m1 is 5, 6, 7, 8, 9, or
 10. 9. Thecompound of claim 7 or 8, wherein m2 is 5, 6, 7, 8, 9, or
 10. 10. Thecompound of claim 7, wherein m1=m2.
 11. The compound of claim 10,wherein each of m1 and m2 is
 6. 12. The compound of claim 7, whereineach of m1 and m2 is
 0. 13. The compound of claim 7, wherein n is 5, 6,7, 8, 9, or
 10. 14. The compound of claim 13, wherein n is
 8. 15. Thecompound of claim 1, wherein X₂ is H, CH₃, or CH₂CH₃.
 16. The compoundof claim 1, wherein X₂ is F_(T).
 17. The compound of claim 1, wherein X₃is F_(T).
 18. The compound of claim 1, wherein each F_(T), when present,is independently a polyfluoroorgano group.
 19. The compound of claim 1,wherein each F_(T), when present, is independently—(O)_(q)—[C(═O)]_(r)—(CH₂)_(o)(CF₂)_(p)CF₃, wherein q is 0, and r is 1,or q is 1, and r is 0; o is from 0 to 2; and p is from 0 to 10; providedthat said compound does not contain —O—O—.
 20. The compound of claim 1,wherein each F_(T) comprises (CF₂)₅CF₃.
 21. The compound of claim 1,wherein X₁ is CH₂CH₃.
 22. The compound of claim 1, wherein said compoundhas a theoretical molecular weight of less than 10,000 Daltons.
 23. Thecompound of claim 1, wherein said compound has a thermal degradationtemperature from 200° C. to 400° C.
 24. A compound of formula (II),

wherein each F_(T) is independently a surface active group selected fromthe group consisting of polydimethylsiloxanes, hydrocarbons,polyfluoroorgano, and combinations thereof; each of X₁, X₂, and X₃ isindependently H, CH₃, CH₂CH₃, or F_(T); each of L₁ and L₂ isindependently a bond, an oligomeric linker, or a linker with twoterminal carbonyls; and each of n1 and n2 is independently an integerfrom 3 to
 50. 25. The compound of claim 24, wherein each of L₁ and L₂ isa bond.
 26. The compound of claim 24, wherein each of L₁ and L₂ is alinker with two terminal carbonyls.
 27. The compound of claim 24,wherein each of L₁ and L₂ is an oligomeric linker.
 28. The compound ofclaim 27, wherein said oligomeric linker comprises (ethylene oxide)_(z),wherein z is an integer from 2 to
 20. 29. The compound of claim 24,having a structure of formula (II-A),

wherein each of m1 and m2 is independently an integer from 0 to
 50. 30.The compound of claim 29, wherein m1 is 5, 6, 7, 8, 9, or
 10. 31. Thecompound of claim 29 or 30, wherein m2 is 5, 6, 7, 8, 9, or
 10. 32. Thecompound of claim 29, wherein m1=m2.
 33. The compound of claim 32,wherein each of m1 and m2 is from 2 to
 6. 34. The compound of claim 33,wherein each of m1 and m2 is
 3. 35. The compound of claim 29, whereinthe sum of n1, n2, m1, and m2 is an integer from 5 to
 15. 36. Thecompound of claim 24, wherein n1 is
 4. 37. The compound of claim 24,wherein n2 is
 5. 38. The compound of claim 24, wherein X₂ is H, CH₃, orCH₂CH₃.
 39. The compound of claim 24, wherein X₂ is F_(T).
 40. Thecompound of claim 24, wherein X₁ is F_(T).
 41. The compound of claim 24,wherein X₃ is F_(T).
 42. The compound of claim 24, wherein each F_(T),when present, is independently a polyfluoroorgano group.
 43. Thecompound of claim 24, wherein each F_(T), when present, is independently—(O)_(q)—[C(═O)]_(r)—(CH₂)_(o)(CF₂)_(p)CF₃, wherein q is 0, and r is 1,or q is 1, and r is 0; o is from 0 to 2; and p is from 0 to 10; providedthat said compound does not contain —O—O—.
 44. The compound of claim 24,wherein each F_(T) comprises —(CF₂)₅CF₃.
 45. A compound of formula (IV):G-(A)_(m)-[B-A]_(n)-B-G  (IV) wherein (i) A comprises a polysiloxane;(ii) B comprises is a bond, an oligomeric linker, or a linker with twoterminal carbonyls; and (iii) G is (a) a surface active group comprisinga polyfluoroorgano group or (b) H; (iv) n is an integer from 1 to 10;and (v) m is 0 or 1; provided that at least one G is said surface activegroup comprising said polyfluoroorgano group.
 46. The compound of claim45, wherein A comprises a triblock copolymer PEG-b-(polysiloxane)-b-PEG.47. The compound of claim 45, wherein B is a bond.
 48. The compound ofclaim 45, wherein B is a linker with two terminal carbonyls.
 49. Thecompound of claim 45, wherein B is norbornene-dicarbonyl orterephthaloyl.
 50. The compound of claim 45, wherein said surface activegroup is a polyfluoroorgano.
 51. The compound of claim 45, wherein saidsurface active group is —(O)_(q)—[C(═O)]_(r)—(CH₂)_(o)(CF₂)_(p)CF₃,wherein q is 0, and r is 1, or q is 1, and r is 0; o is from 0 to 2; andp is from 0 to 10; provided that said compound does not contain —O—O—.52. The compound of claim 45, wherein n is 1 or
 2. 53. The compound ofclaim 45, wherein m is
 0. 54. A composition comprising the compound ofclaim
 45. 55. An admixture comprising a base polymer and from 0.005% to15% (w/w) of the compound of claim 1 or the composition of claim
 54. 56.The admixture of claim 55, wherein said base polymer is selected fromthe group consisting of polyurethanes, polysulfones, polycarbonates,polyesters, polyamides, polyimides, polyetherimides, polyalkylenes,polysilicone, polysaccharides and copolymers thereof and blends thereof.57. The admixture of claim 56, wherein said base polymer is selectedfrom the group consistin of polyethylene, polypropylene, polystyrene,polybutadiene, polyisoprene, poly(acrylonitrile-butadienestyrene),cellulose, cellulose acetates, cellulose diacetates, cellulosetriacetates, polyethylene terephtahate.
 58. The admixture of claim 56,wherein said base polymer is selected from the group consistin ofpolyamides, polyurethanes, polysilicones, polysulfones, polyalkylenes,polyesters, polypeptides, and polysaccharides.
 59. The admixture ofclaim 56, wherein said base polymer is selected from the groupconsisting of polyurethanes, polysulfones, polycarbonates, polyesters,polyamides, polyethylene, polypropylene, polystyrene, polysilicone,poly(acrylonitrile-butadiene-styrene), polybutadiene, polyisoprene,polymethylmethacrylate, polyvinylacetate, polyacrylonitrile, polyvinylcloride, polyethylene terephtahate, cellulose, cellulose acetates, andcellulose di- and tri-acetates.